Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review

Silva, Ana Carolina Bueno; Anchieta, Leni Marcia; Lopes, Marianna Fischer de Paula; Romanelli, Roberta Maia de Castro

doi:10.1016/j.bjid.2018.07.009

Acessibilidade / Reportar erro

Brasil

Brazilian Journal of Infectious Diseases

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Review articles • Braz J Infect Dis 22 (4) • Jul-Aug 2018 • https://doi.org/10.1016/j.bjid.2018.07.009 copy

Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review^☆ ☆ Support - Institutional Scholarship of Federal University of Minas Gerais/Fundação de Amparo a Pesquisa de MInas Gerais (FAPEMIG).

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Background

Technologies and life support management have enhanced the survival of preterm infants. The immune system of newborns is immature, which contributes to the occurrence of healthcare-associated infections. The overlap of several conditions with neonatal sepsis and the difficulty of diagnosis and laboratory confirmation during this period result in a tendency to over-treat neonatal sepsis. The use of antimicrobial agents is a risk factor for multidrug-resistant bacterial infections. This work aimed to perform a systematic review of the relationship between inadequate use of antimicrobial agents and increase in neonatal sepsis related to healthcare assistance, due to bacterial resistance.

Methods

Our population, exposition, comparison, outcome and study type was as follows: P: hospitalized neonates with sepsis diagnosis, E: inappropriate use of antimicrobial agents, C: adequate use of antimicrobial agents or no indication of infection, O: resistant bacterial infection, and S: original studies. We performed searches in the PubMed, Scopus, Virtual Health Library (Scielo, LILACS, and MEDLINE), and Embase without limits on time, language, and the references of the articles found. Fourteen studies were included and assessed using the Grading of Recommendations, Assessment, Development, and Evaluation, Newcastle, and the Strengthening the Reporting of Observacional Studies in Epidemiology methodologies.

Results

All studies found were observational and started with a low-quality evidence level in the Grading of Recommendations, Assessment, Development, and Evaluation.

Conclusions

Despite their low-quality evidence, the studies demonstrated the association between inadequate use of antimicrobial agents and increase of neonatal resistant bacterial healthcare-associated infections in neonatal units. However, there is significant difficulty in conducting high-quality studies in this population due to ethical issues tied to randomized trials. Therefore, new studies should be encouraged to recommend adequate treatment of newborns without increasing the risk of healthcare-associated infections by multidrug-resistant bacteria.

Keywords:
Sepsis; Drug resistance, microbial; Infant, newborn, anti-infective agents

First author (year and publication country)	Type of study	Population	Outcome	Results	Newcasttle Otawa^a a A study can be awarded a maximum of one star for each numbered item within the selection and exposure categories. A maximum of two stars can be given for comparability. For comparability the most important factor was HAI by resistant bacteria.			Imprecision (NNH)^b b NNH, Number of patients Needed to Harm.
					Selection (****)	Outcome (***)	Comparability (**)
Bryan³⁴34 Bryan CS, John JF, Pai MS, Austin TL. Gentamicin vs cefotaxime for therapy of neonatal sepsis. Relationship to drug resistance. Am J Dis Child. 1985;139:1086-9.	Prospective cohort	Lack of data about the total number of hospitalization.	Evaluation of time and number of GNB infection emergence during the replacement of the antibiotic empiric treatment with gentamicin after K. pneumoniae resistant to gentamicin outbreak and the use of cefotaxime as the replaced treatment.	Resistant to 3rd generation cephalosporin GNB appeared faster and seriousness.	**	*	*	-
Calil²2 Calil R, Marba ST, von Nowakonski A, Tresoldi AT. Reduction in colonization and nosocomial infection by multiresistant bacteria in a neonatal unit after institution of educational measures and restriction in the use of cephalosporins. Am J Infect Control. 2001;29:133-8.	Prospective cohort	Phase 1: 67 samples from 31 patients. Phase 2: 342 patients. Phase 3: 891 colonizations of 324 patients. Phase 4: nosocomial infections: 1995: 78; 1996: 74; 1997: 75; 1998: 52; 1999: 57.	Incidence of multidrug resistance considering the period before and after implementation of infection control measures, including restricted use of cefotaxime.	Reduction in the incidence of resistant bacteria infection, from 18 per year to 2 per year, from 1995 to 1999.	***	***	**	NNH = 4.9
Singh³³33 Singh N, Patel KM, Léger M-M, et al. Risk of resistant infections with Enterobacteriaceae in hospitalized neonates. Pediatr Infect Dis J. 2002;21:1029-33.	Prospective cohort	From 240 colonized by resistant Enterobacteria. 34 developed infection.	Risk factors related to multidrug-resistant Enterobacteria infection in patients colonized by these bacteria.	At the multivariate analyzes, the prolonged use of antibiotics was considered as a risk factor, with OR: 1.8 (CI 95%: 1.32-2.44).				NNH = 8.3
Flidel-Ramon²⁸28 Flidel-Rimon O, Friedman S, Gradstein S, Bardenstein R, Shinwell ES. Reduction in multiresistant nosocomial infections in neonates following substitution of ceftazidime with piperacillin/tazobactam in empiric antibiotic therapy. Acta Pædiatr. 2003;92:1205-7.	Prospective cohort	Phase 1: 5661 neonates/year. Phase 2: 6255 neonates/year.	Evaluates the reduction of MR-GNB after replacement of cefotaxime to piperacillin/tazobactam.	Important reduction in incidence of MR-GNB infection.	***	***	**	NNH = 1.85
Pessoa-Silva¹⁵15 Pessoa-Silva CL, Meurer Moreira B, Camara Almeida V, et al. Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a neonatal intensive care unit: risk factors for infection and colonization. J Hosp Infect. 2003;53:198-206.	Prospective cohort	13 ESBL infected patients.	Evaluates risk factors related to ESBL colonization and infection.	Strong relation with infection and colonization OR: 5.19 (CI 95%:1.58-17.08) and presents as a risk factor to colonization the use of cephalosporin + aminoglycosides. OR: 4.69.	***	***	**	-
Linkin³²32 Linkin DR, Fishman NO, Patel JB, Merrill JD, Lautenbach E. Risk factors for extended-spectrum beta-lactamase-producing Enterobacteriaceae in a neonatal intensive care unit. Infect Control Hosp Epidemiol. 2004;25:781-3.	Case control	4 ESBL Enterobacteria infected patients and 6 non-ESBL Enterobacteria infected patients.	Clinical risk factors to develop ESBL infection.	Previous treatment with cephalosporin duration was considered as a risk factor p = 0.2.	**	*	*	-
Crivaro³⁰30 Crivaro V, Bagattini M, Salza MF, et al. Risk factors for extended-spectrum beta-lactamase-producing Serratia marcescens and Klebsiella pneumoniae acquisition in a neonatal intensive care unit. J Hosp Infect. 2007;67:135-41.	Case control	167 patients, including 100 ESBL K. pneumoniae and/or Serratia marcescens infection.	Infected and non-infected patients by GNB producer of ESBL during an outbreak.	Duration of treatment with ampicillin and gentamicin was OR: 1.316 (CI 95%: 1.021-1.695) with p < 0.034.	**	*	-	NNH = 5.1
Huang¹⁷17 Huang Y, Zhuang S, Du M. Risk factors of nosocomial infection with extended-spectrum beta-lactamase-producing bacteria in a neonatal intensive care unit in China. Infection. 2007;35:339-45.	Case control	22 cases and 17 controls.	Risk factors for K. pneumoniae and E. coli producer of ESBL infection.	OR: 12.8 (CI 95%: 1.1-143.8) to the previous use of 3rd generation cephalosporin.	***	***	**	NNH = 2.3
Abdel-Hady⁵5 Abdel-Hady H, Hawas S, El-Daker M, El-Kady R. Extended-spectrum beta-lactamase producing Klebsiella pneumoniae in neonatal intensive care unit. J Perinatol. 2008;28:685-90.	Prospective cohort	473 hospital admissions including 138 proved cases of sepsis related to healthcare assistance.	Neonates infected with Klebisiella pneumoniae and neonates infected with ESBL K. pneumoniae.	The use of oxymin-antibiotics had OR: 4.9 (CI 95%: 1.1-21.5) with p < 0.04.	***	***	**	NNH = 3.7
Le³¹31 Le J, Nguyen T, Okamoto M, McKamy S, Lieberman JM. Impact of empiric antibiotic use on development of infections caused by extended-spectrum beta-lactamase bacteria in a neonatal intensive care unit. Pediatr Infect Dis J. 2008;27:314-8.	Prospective cohort	Phase 1:130 neonates. Phase 2: 120 neonates.	Clinical characteristics after altering the treatment from cefotaxime to trobamycin on empiric treatment to late sepsis.	Significative reduction in ESBL infection. OR: 33.73 (CI 95%: 1.02-1136.2) to the exposure of cephalosporin and an of OR 3.09 (CI 95%: 1.28-7.49) to each additional day using ampicillin and gentamicin and OR: 1.55 (CI 95%: 0.963-2.49) related to the prolonged use of cefotaxime and trobamycin.	***	***	**	NNH = 2.7
Murki¹⁴14 Murki S, Jonnala S, Mohammed F, Reddy A. Restriction of cephalosporins and control of extended spectrum β-lactamase producing gram negative bacteria in a neonatal intensive care unit. Indian Pediatr. 2010;47:785-8.	Prospective cohort	Phase 1:1046 neonates. Phase 2: 1074 neonates.	Clinical characteristics before and after the restriction of cephalosporin use.	22% reduction in ESBL infection (p = 0.035), 30% cefotaxime resistant infection (p = 0.006) and 27% in ciprofloxacine resistant infection (p = 0.01).	***	***	**	NNH = 4.5
Landre-Peigne²⁶26 Landre-Peigne C, Ka AS, Peigne V, Bougere J, Seye MN, Imbert P. Efficacy of an infection control programme in reducing nosocomial bloodstream infections in a Senegalese neonatal unit. J Hosp Infect. 2011;79:161-5.	Prospective cohort	Phase 1: 125 neonates. Phase 2: 148 neonates.	Evaluates the incidence of multidrug-resistant bacteria's and antibiotic use after the implementation of infection control measures.	Despite the suspicious of precocious sepsis, there was a reduction in the treatment number and a significative decrease in the incidence of resistant bacteria (p < 0.001).	***	***	**	NNH = 1.49
Tsai²⁹29 Tsai M-H, Chu S-M, Hsu J-F, et al. Risk factors and outcomes for multidrug-resistant Gram-negative bacteremia in the NICU. Pediatrics. 2014;133:e322-9. https://doi.org/10.1542/peds.2013-1248...	Prospective cohort	70 multidrug resistant GNB infected neonates and 306 infected by other bacteria's type.	Risk factors to multidrug-resistant GNB infection.	3rd generation cephalosporin, vancomycin/teicoplanin and carbapenem used (p < 0.001); time >48 h to adequate the antibiotic (p < 0.001). In multivariate analyses, 3rd generation cephalosporin use OR: 5.97, OR: 5.97 (CI 95%: 2.37-15.08) and carbapenem OR: 3.60 (CI 95%: 1.26-10.29) were associated with increased risk.	***	***	**	NNH = 2.47
Yusef⁴4 Yusef D, Shalakhti T, Awad S, Algharaibeh H, Khasawneh W. Clinical characteristics and epidemiology of sepsis in the neonatal intensive care unit in the era of multi-drug resistant organisms: a retrospective review. Pediatr Neonatol. 2017.	Case control	35 multidrug-resistant bacteria infected neonates (ESBL, MARSA, KPC and MR Acineto baumannii) and 16 non-infected.	Risk factors to multidrug resistant bacteria.	Previous use of vancomycin and meropenem was considered as a risk factor to KPC and MDR - A. baumannii infection (OR: 0.07).	**	**	*	NNH = 2.38

Quality assessment							Quality
Studies	Study design	Methodological bias	Inconsistency	Indirect evidences	Imprecision	Publication bias
Healthcare-associated infections by resistant bacteria
14	10 prospective cohort 04 of case-control	No severe limitation^a a All the studies were observational, which present a greater risk of bias. Although three studies present methodological limitations, nothing was considered as serious to downgrade the score in this item.	Severe inconsistency^b b Once it was not a meta-analysis, I 2 was not calculated. The inconsistency was assessed through measures of effect and confidence interval in seven studies that showed an association between antimicrobial use and increased nosocomial infection by multi-resistant bacteria. One study showed a low inconsistency because the confidence interval crosses the number 1 and other three studies presented very wide confidence intervals.	No important indirect evidence^c c Although the studies present different methodological differences between themselves and based on PECO question of the review, no serious indirect evidence was observed, since the result and the population are the same in all studies.	Severe imprecision^d d The absolute effect (difference between the exposed and non-exposed groups) was considered and calculated for the studies that presented the effect measure. The Number of patients Needed to Harm (NNH) was calculated, which presented important variation, suggesting imprecision of the articles.	No important publication bias^e e Despite the few studies found, an extensive search was conducted in several databases and references of articles studied. Only one study was excluded by language, but its English summary showed results compatible with the others.	Very low^f f The GRADE quality of evidence in the review was very low, since it has already begun with a low level evidence once only observational studies were found.

Brazilian Society of Infectious Diseases Rua Augusto Viana, SN, 6º., 40110-060 Salvador - Bahia - Brazil, Telefax: (55 71) 3283-8172, Fax: (55 71) 3247-2756 - Salvador - BA - Brazil
E-mail: bjid@bjid.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Conflicts of interest

The authors declare no conflicts of interest.

Brasil

Brasil

Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review☆ ☆ Support - Institutional Scholarship of Federal University of Minas Gerais/Fundação de Amparo a Pesquisa de MInas Gerais (FAPEMIG).

ABSTRACT

Background

Methods

Results

Conclusions

Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review^☆ ☆ Support - Institutional Scholarship of Federal University of Minas Gerais/Fundação de Amparo a Pesquisa de MInas Gerais (FAPEMIG).